Background: Acute vascular endothelial dysfunction is a central event in the pathogenesis of sepsis and leads to increasing vascular leak, tissue oedema and compromising regional perfusion in critical organs. While bacteria remain the primary cause of sepsis, current etiologic evidence indicates that the incidence of fungal infection in septic patients is increasing at a rapid rate. There is a paucity of information on the molecular mechanism through which fungus interact with endothelial cells, specifically by the commensal yet opportunistic pathogen, Candida albicans.
Aims: Our aim is to elucidate the factors by which C. albicans interacts with vascular endothelial cells to result in disseminated candidiasis.
Methods: Human endothelial cells were sheared at physiological rates and fungal attachment was examined through phase-contrast and immunofluorescence microscopy. Changes in vascular permeability were measured by transwell paracellular permeation.
Results: C. albicans binds to both static (9.61 yeast cells/mm2) and sheared (84.41 yeast cells/mm2) human endothelial cells, although binding was significantly stronger to sheared endothelial cells (p< 0.0001) and with human plasma (p< 0.05). Binding was dose-dependently inhibited using the αVβ3 antagonist, cilengitide (23.98 yeast cells/mm2 with drug, 84.41 yeast cells/mm2 without drug, p< 0.005). Attachment resulted in disturbances in endothelial barrier integrity, as determined by loss of tight junction protein staining and an increase in permeability. Interestingly and consistent with previous observations, using immunofluorescence we demonstrated that C. albicans expresses an integrin αVβ3-like protein on its surface which we believe binds directly to plasma fibrinogen and cross-links the fungus to human endothelial cell αVβ3.
Conclusions: Our data for the first time demonstrates a mechanism through which C. albicans attaches to the vascular endothelium, to promote further dissemination upon barrier penetration. Additionally, inhibition of C. albicans binding to endothelial αVβ3 using cilengitide prevents endothelial dysfunction and therefore may present as a novel therapeutic approach for the treatment of fungal sepsis.
To cite this abstract in AMA style:Nader D, Curley G, Kerrigan S. Candida albicans Expresses an Integrin-like Protein that Is Involved in Yeast Adhesion to Endothelial Cells [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/candida-albicans-expresses-an-integrin-like-protein-that-is-involved-in-yeast-adhesion-to-endothelial-cells/. Accessed October 26, 2020.
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